RSS-Feed abonnieren
Bitte kopieren Sie die angezeigte URL und fügen sie dann in Ihren RSS-Reader ein.
https://www.thieme-connect.de/rss/thieme/de/10.1055-s-00000083.xml
Synlett 2012; 23(13): 1923-1926
DOI: 10.1055/s-0031-1290694
DOI: 10.1055/s-0031-1290694
letter
General Synthetic Approach to 2-Phenolic Adenine Derivatives
Weitere Informationen
Publikationsverlauf
Received: 05. Mai 2012
Accepted after revision: 14. Mai 2012
Publikationsdatum:
04. Juli 2012 (online)
![](https://www.thieme-connect.de/media/synlett/201213/lookinside/thumbnails/10.1055-s-0031-1290694-1.jpg)
Abstract
A simple and general ‘one-pot’ procedure for the synthesis of 2,9-diarylpurines with one or multiple hydroxyl groups in the 2-aryl unit is described, from the reaction of 5-amino-4-amidinoimidazoles with phenolic aldehydes.
-
References and Notes
- 1 Legraverend M, Grierson DS. Bioorg. Med. Chem. 2006; 14: 3987
- 2a Gupte A, Boshoff HI, Wilson DJ, Neres J, Labello NP, Somu RV, Xing C, Barry CE. III, Aldrich CC. J. Med. Chem. 2008; 51: 7495
- 2b Neres J, Labello NP, Somu RV, Boshoff HI, Wilson DJ, Vannada J, Chen L, Barry CE. III, Bennett EM, Aldrich CC. J. Med. Chem. 2008; 51: 5349
- 2c Long MC, Shaddix SC, Moukha-Chafiq O, Maddry JA, Nagy L, Parker WB. Biochem. Pharmacol. 2008; 75: 1588
- 2d Bisseret P, Thielges S, Bourg S, Miethke M, Marahiel MA, Eustachea J. Tetrahedron Lett. 2007; 48: 6080
- 2e Qiao C, Gupte A, Boshoff HI, Wilson DJ, Bennett EM, Somu RV, Barry CE, Aldrich CC. J. Med. Chem. 2007; 50: 6080
- 2f Rai D, Johar M, Srivastav NC, Manning T, Agrawal B, Kunimoto DY, Kumar R. J. Med. Chem. 2007; 50: 4766
- 2g Qiao C, Wilson DJ, Bennett EM, Aldrich CC. J. Am. Chem. Soc. 2007; 129: 6350
- 2h Vannada J, Bennett EM, Wilson DJ, Boshoff HI, Barry CE, Aldrich CC. Org. Lett. 2006; 8: 4707
- 2i Somu RV, Wilson DJ, Bennett EM, Boshoff HI, Celia L, Beck BJ, Barry CE, Aldrich CC. J. Med. Chem. 2006; 49: 7623
- 2j Bennett EM, Barry CE, Aldrich CC. J. Med. Chem. 2006; 49: 31
- 3a Bakkestuen AK, Gundersen L.-L, Utenova BT. J. Med. Chem. 2005; 48: 2710
- 3b Braendvang M, Gundersen L.-L. Bioorg. Med. Chem. 2007; 15: 7144
- 3c Braendvang M, Gundersen L.-L. Bioorg. Med. Chem. 2005; 13: 6360
- 3d Bakkestuen AK, Gundersen L.-L, Petersen D, Utenova BT, Vik A. Org. Biomol. Chem. 2005; 3: 1025
- 3e Pathak AK, Pathak V, Seitz LE, Suling WJ, Reynolds RC. J. Med. Chem. 2004; 47: 273
- 3f Barrow EW, Westbrook L, Bansal N, Suling WJ, Maddry JA, Parker WB, Barrow WW. J. Antimicrob. Chemother. 2003; 52: 801
- 3g Andersen G, Gundersen L.-L, Nissen-Meyer J, Rise F, Spilsberg B. Bioorg. Med. Chem. Lett. 2002; 12: 567
- 3h Gundersen L.-L, Nissen-Meyer J, Spilsberg B. J. Med. Chem. 2002; 45: 1383
- 3i Scozzafava A, Mastrolorenzo A, Supuran CT. Bioorg. Med. Chem Lett. 2001; 11: 1675
- 3j Bakkestuen AK, Gundersen L.-L, Langli G, Liu F, Nolsoe JM. J. Bioorg. Med. Chem. Lett. 2000; 10: 1207
- 3k Scozzafava A, Mastrolorenzo A, Supuran CT. Bioorg. Med. Chem. Lett. 2001; 11: 1675
- 4 Correia C, Carvalho MA, Proença MF. Tetrahedron 2009; 65: 6903
- 5a For a recent review, see: Legraverend M. Tetrahedron 2008; 64: 8585
- 5b Ibrahim N, Legraverend M. J. Org. Chem. 2009; 74: 463
- 5c Alves MJ, Booth BL, Freitas AP, Proença MF. J. Chem. Soc., Perkin Trans. 1 1992; 913
- 5d Booth BL, Dias AM, Proença MF. J. Chem. Soc., Perkin Trans. 1 1992; 2119
- 5e Alves MJ, Booth BL, Proença MF. J. Heterocycl. Chem. 1994; 31: 345
- 5f Booth BL, Coster RD, Proença MF. Synthesis 1988; 389
- 5g Alves MJ, Booth BL, Carvalho MA, Pritchard RG, Proença MF. J. Heterocycl. Chem. 1997; 34: 739
- 5h Al-Azmi A, Booth BL, Carpenter RA, Carvalho MA, Marrelec E, Pritchard RG, Proença MF. J. Chem. Soc., Perkin Trans. 1 2001; 2532
- 5i Booth BL, Cabral IM, Dias AM, Freitas AP, Matos-Beja AM, Proença MF, Ramos-Silva M. J. Chem. Soc., Perkin Trans. 1 2001; 1241
- 5j Carvalho MA, Esteves TM, Proença MF, Booth BL. Org. Biomol. Chem. 2004; 2: 1019
- 5k Carvalho MA, Álvares Y, Zaki ME, Proença MF, Booth BL. Org. Biomol. Chem. 2004; 2: 2340
- 5l Alves MJ, Carvalho MA, Carvalho S, Dias AM, Fernandes FH, Proença MF. Eur. J. Org. Chem. 2007; 4881
- 6 Procedure for the Synthesis of Imine 4a (Scheme 1) To a stirred suspension of imidazole 1a (0.14 g, 0.49 mmol) in EtOH (0.4 mL), aldehyde 2a (0.09 g, 1.1 equiv) and TFA (75 μL, 2 equiv) were added at 0 °C. A yellow solution developed, and a yellow solid started to precipitate after 25 min. When the TLC indicated the absence of starting material (4 h), EtOH was added (0.8 mL), and the yellow solid was filtered. The solid was washed with EtOH and Et2O and identified as compound 4a (0.22 g, 0.40 mmol, 82%); mp 124–126 °C. IR (mull): 3498, 3352, 3210, 1665, 1626, 1604, 1586, 1521 cm–1. 1H NMR (300 MHz, DMSO-d 6): δ = 1.62 (s, 6 H, CH2), 2.37 (s, 3 H, CH3), 3.58 (br s, 4 H, CH2), 6.82 (s, 2 H, ArH), 7.30–7.45 (m, 4 H, ArH), 8.17 (s, 2 H, 2-H, N=CH), 8.80–9.60 (m, 5 H, NH, HO, D2O exchangeable). Anal. Calcd for C23H25N5O3·TFA·H2O: C, 54.44; H, 5.08; N, 12.70. Found: C, 54.68; H, 5.41; N, 12.45
- 7a Method i Aldehyde 2a (0.07 g, 1.0 equiv) and TFA (40 μL,1.3 equiv) were added to a stirred suspension of imidazole 1a (0.11 g, 0.40 mmol) in EtOH (2.0 mL) at r.t. The yellow solution became light yellow, and when TLC showed the absence of imine 4 (5 d), the solution was concentrated in the rotary evaporator. The off-white solid was filtered, washed with EtOH and Et2O and identified as compound 5c (0.09 g, 0.16 mmol, 41%)
- 7b Method iiA yellow ethanolic solution of 4a (0.09 g, 0.16 mmol) was stirred at 8 °C until TLC showed the absence of starting material (10 d). The solution was concentrated in the rotary evaporator leading to an off-white solid that was filtered and washed with Et2O and identified as compound 5c (0.08 g, 0.15 mmol, 91%); mp 218–220 °C. IR (mull): 3535, 3202, 1679, 1613, 1530 cm–1. 1H NMR (300 MHz, DMSO-d 6): δ = 1.69 (s, 6 H, CH2), 2.39 (s, 3 H, CH3), 3.70 (m, 4 H, CH2), 5.71 (t, 1 H, J = 4.8 Hz, 2-H), 6.28 (s, 2 H, ArH), 7.40–7.46 (m, 4 H, ArH), 7.88 (s, 1 H, 8-H), 8.07 (d, 1 H, J = 4.8 Hz, NH, D2O exchangeable), 8.23 (br s, 1 H, HO, D2O exchangeable), 8.88 (d, 1 H, J = 4.8 Hz, NH, D2O exchangeable), 8.99 (s, 2 H, HO, D2O exchangeable). 13C NMR (75 MHz, DMSO-d 6): δ = 20.62 (CH3), 23.32, 25.80, 48.82, 64.77 (2-C), 105.12, 110.60, 124.14, 129.16, 130.32, 130.88, 133.39, 135.14 (8-C), 138.65, 145.73, 145.84, 150.00. Anal. Calcd for C23H25N5O3·TFA·2.1H2O: C, 52.56; H, 5.29; N, 12.26. Found: C, 52.55; H, 5.10; N, 12.07
- 8 Procedure for the Synthesis of Purine 6f (Table 1) Aldehyde 2g (0.18 g, 1.1 equiv) and TFA (166 μL, 1.3 equiv) were added to a stirred suspension of imidazole 1b (0.30 g, 1.08 mmol) in EtOH (0.3 mL) at r.t. during 1 d. Then, the solvent was removed in the rotary evaporator, and DMSO (0.3 mL) was added to the crude solid followed by Et3N (1.35 mL, 10 equiv), and the reaction was stirred at 40 °C during 6 d. Addition of H2O and cooling for 10 min led to a brown solid that was filtered and washed with H2O and Et2O (0.42 g). The brown solid was purified by dry flash chromatography on silica gel using 500 mL of Et2O as eluent to give an off-white solid identified as 6f (0.25 g, 0.60 mmol, 59%); mp >300 °C. IR (mull): 3550, 3465, 3337, 3101, 1637, 1624, 1581, 1528 cm–1. 1H NMR (300 MHz, DMSO-d 6): δ = 2.41 (s, 3 H, CH3), 3.85 (s, 4 H, CH2), 4.30 (br s, 4 H, CH2), 6.36 (d, 1 H, J = 9.0 Hz, ArH), 7.43 (d, 2 H, J = 8.4 Hz, ArH), 7.64 (d, 2 H, J = 8.7 Hz, ArH), 7.68 (d, 1 H, J = 9.0 Hz, ArH), 8.24 (br s, 1 H, HO, D2O exchangeable), 8.45 (s, 1 H, 8-H), 9.16 (br s, 1 H, HO, D2O exchangeable), 13.45 (s, 1 H, HO, D2O exchangeable). 13C NMR (75 MHz, DMSO-d 6): δ = 20.64 (CH3), 45.52, 66.13, 107.05, 111.53, 117.57, 119.45, 123.82, 130.17, 131.99, 132.69, 137.77, 139.18 (8-C), 148.54, 148.93, 149.36, 152.66, 158.86 (2-C). Anal. Calcd for C22H21N5O4·0.5H2O: C, 61.68; H, 5.14; N, 16.36. Found: C, 61.75; H, 5.06; N, 16.20
Procedure for the Synthesis of Dihydropurine 5c (Scheme 1)